1. Field of the Invention
The present invention relates to a novel azetidine derivative, a bifidobacterium division-promoting composition containing the azetidine derivative as an active component, and a process for production thereof.
2. Description of the Related Art
Bifidobacteria are indigenous to healthy living bodies. One gram of fecal matter contains 10,000,000,000 or more bifidobacterium cells. The bifidobacteria produce a varieties of short-chain fatty acids which promote effectively absorption of nutrient sources, water, and electrolytes by the intestinal epithelial cells. Further, the bifidobacteria are known to augment the intestinal immunizing function. The bifidobacteria having such useful properties may decline extremely depending on changes of environmental conditions, external factors, aging, and other factors of the host living body to result in disorder of bowel action. In such a case, the decreased or declined bifidobacteria which are indigenous to the living body need to be activated. The microorganism multiplies by repeating division of cells. An index for the multiplication is a doubling time, which is a time length for one cell generation from a cell division to the next cell division. For example, the average doubling time is 17 minutes for Escherichia coli, 20 minutes for lactic acid bacteria, 30 minutes for Bacillus bacteria, and 120 minutes for yeast. Although quinolone compounds and the like coenzymes are well known to promote the cell division, it is not easy to augment further the inherent multiplication ability of microorganisms. Moreover, the microorganism may lose its growth activity in the case where the microorganism is kept outside its optimum environment conditions: for example, in the case where anaerobic bifidobacterium is kept under aerobic conditions for a long time. In the intestine of a living body also, the bifidobacteria and other bacteria in the intestine content may decline according to disease, environmental change, or aging. Even when the number of the bifidobacterium cells is kept normal, the bowel action may be disordered. In such cases, the multiplication activity of the bifidobacteria is considered to have dropped. To restore the activity, supply of a multiplication-promoting factor for the bifidobacteria can be an effective measure.
Many bifidobacterium multiplication-promoting factors have been reported. Ten and several glycosides typified by oligosaccharides have been commercialized. These bifidobacterium multiplication-promoting substances are characterized mainly by their properties as selective nutrient sources, and are not necessarily sufficient for activation of bifidobacteria having declined multiplication activities.
The known bifidobacterium multiplication factors exert mild actions, and require long time, after administration, in producing the effect of bifidobacterium multiplication, disadvantageously.
Under such circumstances, a medicine is demanded which can be delivered stably to the intestine to promote specifically the multiplication of bifidobacteria in individual bodies with immediate effect.
The inventors of the present invention discovered a novel substance having an estimated molecular weight ranging from 800 to 900 and being capable of promoting the divisional multiplication of various bifidobacteria, including Bifidobacterium longum, B.breve, A.infantis, and B.adolescentis in metabolites formed by Bacillus mesentericus (JP-A-5-344882). The inventors of the present invention found further a novel azetidine derivative of a molecular weight of 90 having bifidobacterium multiplication-promoting activity in a supernatant of a culture medium of Bacillus mesentericus. The inventors of the present invention established a process for production thereof. Thus the present invention has been accomplished.